PROPOSAL (Adapted from the applicant's abstract): DHEA declines dramatically with age. Low DHEA levels have been found to correlate with sarcopenia and osteopenia. It is, therefore, postulated that many physiologic changes of aging are secondary to the decline in DHEA. Thus, the objective of the proposed research is to evaluate the effect of DHEA replacement on age-related changes in body composition, muscle function and metabolism, and bone mass in healthy older adults. The specific aims are to evaluate the effects of six months DHEA replacement (50 mg/d) alone, or in combination with resistance exercise training on: a) total body fat content and lean body mass [evaluated by dual energy x-ray abosorptiometry (DEXA)], intraabdominal fat volume and thigh muscle area [measured by magnetic resonance imaging (MRI)], and muscle protein synthesis rate (assessed by stable isotopes); b) bone mineral density (BMD) of the total body, lumbar spine, and hip (evaluated by DEXA) and biochemical markers of bone turnover; and c) insulin sensitivity (evaluated by the euglycemic-hyperinsulinemic pancreatic clamp). It is hypothesized that DHEA administration will increase muscle and bone mass, decrease visceral fat mass, and increase insulin sensitivity and that these effects will be additive or synergistic with exercise. Healthy but sedentary subjects (60 men and 60 women), aged 65-78 years old, will be randomized to receive either DHEA, 50 mg/d, or placebo and to participate in either supervised or home exercise training programs. The supervised exercise program will consist of resistance training designed to increase muscle mass, strength, and bone mass, and decrease fat mass. The goal of this research is to provide information on the potential role of DHEA replacement therapy in maintaining the physical health and functional capacity of older people. It will serve as the basis for future studies of DHEA replacement as potential adjunct to the restoration of functional independence in frail older adults. This research and the proposed career development plan shall provide Dr. Villareal the opportunity to develop his capabilities in conducting patient-oriented research and independence as an investigator.